The volume of research directed towards understanding the causes and finding a cure for cancer has greatly increased in the last ten years as a result of increased public concern with the disease. An outgrowth of this research has been the discovery and utilization of a large number of anti-cancer drugs. A common feature of these new drugs is their cytotoxic activity, i.e., they act by killing the cell.
The use of cytotoxic drugs has been a typical first step in the chemotherapeutic treatment of diseases caused by an aggressive cell. This was the case, for example, in the early treatment of tuberculosis, a disease which has now been largely conquered but which was once as dreaded as cancer is today.
As indicated above, cytotoxic agents act by killing cells. Unfortunately, they are not selective and attack healthy or normal cells as well as foreign or diseased ones. Nevertheless, using such agents, skilled specialists were able to add 10-15 years to the life expectancy of persons afflicted with tuberculosis. However, a price had to be paid as the patient suffered terribly from the treatments with these toxic agents. For example, vomiting, hair loss, loss of teeth and other effects had to be endured.
In view of the great shortcomings associated with the use of cytotoxic agents, it could not be said that tuberculosis was curable until non-cytotoxic antibiotic drugs capable of selectively attacking the tuberculosis bacillus became available. Such drugs could be readily used by even general practitioners in relatively simple schemes of treatment. As a result, tuberculosis today has largely been eliminated.
The chemotherapy of cancer is presently limited to cytotoxic drugs that kill normal cells even as they attack the tumor cells. For certain kinds of cancer, skilled specialists using these agents, typically in combinations, have been able to maintain patients relatively free from disease for periods of ten to fifteen years. However, the patient undergoing treatment with these drugs has had to endure great suffering because the cytotoxic agents are severely toxic. Furthermore, the complexity of the treatments preclude their successful use by all but the most highly skilled physicians having access to the best medical facilities. Obviously, many of those who are afflicted with cancer, particularly in underdeveloped countries, do not have access to this kind of treatment. As a result, no one is yet prepared to characterize the limited success achieved using these drugs representing a cure for the cancer involved. That must await the availability of non-toxic drugs that can be readily employed by any physician.
In addition to leading to the discovery of additional cytotoxic agents to be added to the chemical arsenal of anti-cancer drugs, the increased research of recent years has lead to discoveries which are laying the groundwork for a fundamental understanding of the nature of cancer. Out of that research has emerged the concept that the main biological and biochemical differences between a cancer cell and a normal cell are found in the plasma membrane and the cytoskeletal system of contractile microfilaments which connect the plasma membrane with the cell nucleus. It has been postulated that the process by which a normal cell is transformed by a virus or chemical carcinogen to a tumor cell involves a disorganization of the cytoskeletal system of contractile filaments.
Another discovery has been that cancerous cells lack the property of "contact inhibition" that is exhibited by normal cells. Contact inhibition is the property of normal cells when in contact that is manifest by the cessation of cell movement, cell growth and cell division. Because they lack this property, cancer cells when in contact continue to grow and divide. As a result, the cancer cells are highly invasive of adjacent normal tissue. Furthermore, the lack of contact inhibition can result in metastasis, the occurrence of secondary tumors at other body locations caused by tumor cells released into the blood stream.
An important recent discovery has been the observation that tumor cells can be caused to undergo a "reverse transformation" in which the cells take on a morphology akin to that of normal cells in that the cytoskeletal system of contractile filaments in the cells is reorganized and the property of contact inhibition is restored by treatment with dibutyryl cyclic AMP. Cyclic AMP is an agent that naturally occurs in low concentration in cells. However, it serves many cellular functions and, therefore, cannot be administered to humans in a dosage sufficient to restore contact inhibition in cancer cells. This observation has spurred the hope that a specific agent can be found which will induce reverse transformation in cancer cells and restore contact inhibition. Such an agent would be expected to arrest tumor growth and perhaps lead to a slow regression of the tumor by gradual replacement of the tumorous cells with healthy ones.
In view of the state of the art summarized above, one object of the present invention is to provide a new treatment for cancer in mammals, and particularly to treat cancer in humans.
Another object of this invention is to provide a non-cytotoxic chemotherapy for cancer.
Yet another object of this invention is to provide an improved method for causing reverse transformation of cancer cells.
A further object of this invention is to provide a method for imparting the property of contact inhibition to cancer cells.